A preliminary mutation analysis of phenylketonuria in southwest Iran

Area of Science:

• Genetics
• Metabolic Disorders
• Molecular Biology

Background:

• Phenylketonuria (PKU) is a significant autosomal recessive metabolic disorder.
• Mutations in the phenylalanine hydroxylase (PAH) gene are the primary cause of PKU.
• Understanding the genetic basis of PKU is crucial for diagnosis and management.

Purpose of the Study:

• To identify mutations in exons 6, 7, and 10-12 of the PAH gene in PKU patients from southwest Iran.
• To characterize the mutation spectrum and genotype distribution in this specific population.
• To investigate novel sequence variants and polymorphisms within the PAH gene.

Main Methods:

• Direct sequencing of targeted PAH gene exons (6, 7, 10-12) in 40 PKU patients.
• Clinical and biochemical confirmation of PKU diagnosis.
• Analysis of identified mutations, genotypes, and sequence variants.

Main Results:

• Thirteen distinct PAH mutations were identified, including a novel variant Q375R (c.1124A>G).
• Twenty-three different genotypes were associated with the identified mutations.
• Seven polymorphisms and three novel variants were also found in PAH intron regions.
• A mutation detection rate of 53.75% was achieved, confirming a high mutation spectrum.

Conclusions:

• The study identified a significant number of PAH mutations in Iranian PKU patients, highlighting genetic heterogeneity.
• The findings support a high mutation spectrum in southwest Iran, potentially due to ethnic diversity.
• Molecular characterization of PAH mutations is essential for understanding PKU prevalence and for genetic counseling.